Interferons of types I and II differ not only antigenically and physico-chemically, but also in properties related to their receptor specificity. Our results indicate that cell surface changes that cause resistance of L-1210 cells to type I interferon and lack of specific binding of this interferon, do not impede sensitivity to type II interferon. We propose to study the role of specific cell membrane glycoprotein components that are involved in interaction with both types of interferon by isolating such components and investigating their properties. We will carry out binding studies using radiolabeled interferons and cells sensitive and resistant to either of the two interferon types, to correlate interferon sensitivity to parameters of specific binding, such as number of binding sites, affinity constants, or cooperativity of binding. We will separate cell membrane components of sensitive and resistant cells to establish whether different types of interferon bind to different membrane components and whether differences in interferon sensitivity can be correlated with distinct qualitative and/or quantitative changes in cell membrane glycoconjugates. We will carry out chemical and enzymatic analyses of such components to precisely define those structures that are involved in interaction with each interferon. Finally we will chemically or enzymatically modify structures involved in interferon binding, to characterize those constituents that are necessary for interaction with the different interferon molecules and thus for proper functioning of both types of interferon receptors.